1.Protective effect and mechanism of icariin against carbon tetrachloride-induced acute liver injury in mice
Dongyan XIAO ; Wei HE ; Zhiying XIAO ; Yue LIAO ; Jiahao MAO ; Yihuai HE ; Zhigang JIANG
Chinese Journal of Tissue Engineering Research 2024;28(23):3654-3660
		                        		
		                        			
		                        			BACKGROUND:Icariin,with antiinflammatory,antioxygenatory and immunoregulatory effects,can be a potential drug for preventing and treating acute liver injury. OBJECTIVE:To investigate the protective effect and possible mechanism of icariin in mice with acute liver injury induced by carbon tetrachloride. METHODS:Thirty-two Kunming mice were equally and randomly divided into the following groups:normal,model,low-dose icariin and high-dose icariin groups.The low-and high-dose icariin groups were continuously gavaged with icariin(100 and 200 mg/kg,respectively)once a day for 7 continuous days.The normal group and model group were injected with physiological saline(10 mL/kg)at the same time point.After the last administration,all the groups except for the normal group were injected with carbon tetrachloride to induce acute liver injury.The mice were killed 24 hours later,and the liver index was detected.Serum levels of alanine aminotransferase and aspartate aminotransferase were detected by automated biochemical analysis.Tumor necrosis factor α and interleukin 6 levels in serum were detected using ELISA.The levels of superoxide dismutase,glutathione peroxidase and malondialdehyde in liver tissue were detected through a reagent kit.The histopathology changes of the liver were observed by hematoxylin-eosin staining.TUNEL method was used to detect the apoptosis in hepatocytes.Western blot was performed to detect the expression levels of glucose-regulated protein 78 kDa,endoplasmic reticulum stress-related protein(C/-EBP homologous protein),mixed lineage kinase domain-like protein and Caspase-3 in liver tissue. RESULTS AND CONCLUSION:Compared with the normal group,the liver index and serum levels of alanine aminotransferase,aspartate aminotransferase,tumor necrosis factor α and interleukin 6 were increased in the model group(P<0.05).Compared with the model group,the above indexes were decreased in the low-dose and high-dose icariin groups(P<0.05).Compared with the normal group,the activities of superoxide dismutase and glutathione peroxidase in the liver tissue of mice were decreased in the model group(P<0.05)and the level of malondialdehyde was increased(P<0.05).Compared with the model group,the activities of superoxide dismutase and glutathione peroxidase were increased in the low-and high-dose icariin groups(P<0.05)and the level of malondialdehyde was decreased(P<0.05).Hematoxylin-eosin and TUNEL staining showed that mice in the model group had severe structural destruction of liver tissue,extensive necrosis of hepatocytes and high apoptotic rate of hepatocytes,while the structural destruction of liver tissue and the area of necrosis of hepatocytes in the low-and high-dose icariin groups were significantly milder than those in the model group,and the apoptotic rate of hepatocytes was lower than that in the model group(P<0.05).Western blot assay showed that the protein expression of glucose-regulated protein 78 kDa,C/-EBP homologous protein,mixed lineage kinase domain-like protein and Caspase-3 in liver tissue of mice in the model group was increased compared with that in the normal group(P<0.05),while the expression levels of these proteins in liver tissue of mice were significantly reduced after low-and high-dose icariin intervention(P<0.05).To conclude,icariin can produce a protective effect against carbon tetrachloride-induced acute liver injury,and its mechanism may be related to the regulation of endoplasmic reticulum stress and reduction of programmed necrosis.
		                        		
		                        		
		                        		
		                        	
3.A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer
Haoqin JIANG ; Wei CHEN ; Jun HE ; Hong JIANG ; Dandan LIU ; Min LIU ; Mianyang LI ; Zhigang MAO ; Yuling PAN ; Chenxue QU ; Linlin QU ; Dehua SUN ; Ziyong SUN ; Jianbiao WANG ; Wenjing WU ; Xuefeng WANG ; Wei XU ; Ying XING ; Chi ZHANG ; Lei ZHENG ; Shihong ZHANG ; Ming GUAN
Chinese Journal of Laboratory Medicine 2023;46(3):265-273
		                        		
		                        			
		                        			Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.
		                        		
		                        		
		                        		
		                        	
4.Analysis on incidence, mortality and disease burden of acute myocardial infarction in Qingdao, 2014-2020
Xiaohui SUN ; Haiping DUAN ; Canqing YU ; Wenzhong ZHANG ; Jing ZHANG ; Xuefen YANG ; Hua ZHANG ; Xiaojia XUE ; Yuanyuan ZHAO ; Zengzhi ZHANG ; Jintai ZHANG ; Conglin MAO ; Zhigang ZHU ; Kang WANG ; Haiyan MA ; Xiaoyan ZHENG ; Hongxuan YAN ; Shaojie WANG ; Feng NING
Chinese Journal of Epidemiology 2023;44(2):250-256
		                        		
		                        			
		                        			Objective:To describe the characteristics and change trends of incidence, mortality and disease burden of acute myocardial infarction (AMI) in Qingdao from 2014 to 2020.Methods:We analyzed the incidence data of AMI retrieved from Qingdao Chronic Diseases Surveillance System. The average annual percent change (AAPC) of morbidity and mortality of AMI were evaluated by using Joinpoint log-linear regression model. Disability adjusted life year (DALY) was used to estimate disease burden of AMI in Qingdao.Results:A total of 70 491 AMI cases and 50 832 deaths of AMI occurred in Qingdao from 2014 to 2020. The age-standardized morbidity and mortality were 54.71/100 000 and 36.55/100 000, respectively. During 2014-2020, the AAPC of age-standardized morbidity was 2.86% (95% CI: 0.42%-5.35%), and 4.30% (95% CI: 1.24%-7.45%) in men and 0.78% (95% CI: -0.89%-2.47%) in women, respectively. The log-linear regression model showed that age-standardized morbidity in age groups 30-39, 40-49 years increased rapidly, with the AAPCs of 8.92% (95% CI: 2.23%-16.06%) and 6.32% (95% CI: 3.30%-9.44%), respectively. The trend was also observed in age groups 30-39, 40-49 and 50-59 years in men, with the AAPCs of 11.25% (95% CI: 3.54%-19.54%), 6.73% (95% CI: 2.63%-10.99%) and 6.72% (95% CI: 2.98%-10.60%), respectively. There was no significant change in age-standardized mortality. The DALY rate increased from 7.49/1 000 in 2014 to 8.61/1 000 in 2020, with the AAPC of 1.97% (95% CI: 0.36%-3.60%). Conclusions:The age-standardized morbidity of AMI in men increased in Qingdao, especially in those aged 30-49 years, while age-standardized mortality rate of AMI was relatively stable from 2014 to 2020. The burden of disease of AMI increased in both men and women.
		                        		
		                        		
		                        		
		                        	
5.Chinese thoracic surgery experts consensus on postoperative follow-up plans for esophageal squamous cell carcinoma
Longqi CHEN ; Xiaofei LI ; Jianhua FU ; Song ZHAO ; Yin LI ; Yousheng MAO ; Shuoyan LIU ; Zhentao YU ; Lijie TAN ; Hui LI ; Yongtao HAN ; Chun CHEN ; Mingqiang KANG ; Jian HU ; Zhigang LI ; Hecheng LI ; Renquan ZHANG ; Shidong XU ; Linyou ZHANG ; Kaican CAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(02):141-149
		                        		
		                        			
		                        			Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.
		                        		
		                        		
		                        		
		                        	
6.Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11
Chenyang QI ; Liping ZOU ; Suxia WANG ; Xing MAO ; Yuan HU ; Jiaoyu SHI ; Zhigang ZHANG ; Huijuan WU
Cancer Research and Treatment 2022;54(1):182-198
		                        		
		                        			 Purpose:
		                        			The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. 
		                        		
		                        			Materials and Methods:
		                        			In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. 
		                        		
		                        			Results:
		                        			Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. 
		                        		
		                        			Conclusion
		                        			Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment. 
		                        		
		                        		
		                        		
		                        	
7.Effects of overexpression of human vascular endothelial growth factor 165 and human tissue inhibitor of metalloproteinase 1 on rats with myocardial infarction
Yanqiu SONG ; Yongmin MAO ; Hua GENG ; Ying ZHANG ; Ying SHI ; Min REN ; Meilin XU ; Zhigang GUO
Chinese Journal of Emergency Medicine 2021;30(3):293-300
		                        		
		                        			
		                        			Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGF 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism. Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGF 165 group, Ad-hTIMP-1 group and Ad-hVEGF 165+Ad-hTIMP-1 group (hVEGF 165+hTIMP-1) ( n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference t-test. Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGF 165-hTIMP-1 group were significantly increased (both P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both P<0.05). LVEF and LVFS in the hVEGF 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGF 165 group (64.65±4.00) %, (30.95±2.57) % (both P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-Track group ( P<0.01 or P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGF 165-hTIMP-1 group were increased than those in the Ad-Track group ( P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-hVEGF 165 group (both P<0.05). There was no statistically difference in the mRNA expression of Bax, Caspase-3, Bad, and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). The protein expression of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.01), and the protein expression of Bcl-2 in the hVEGF 165-hTIMP-1 group was increased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.05). There were no statistically differences in the protein expression of Bax, Caspase-3 and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). Conclusions:Ad-hVEGF 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGF 165 and hTIMP-1 may have a synergistic effect on MI.
		                        		
		                        		
		                        		
		                        	
8.Contribution of measles virus IgG antibody avidity assay to the identification of measles cases
Yaxing DING ; Naiying MAO ; Wenbo XU ; Zhigang GAO ; Ying ZHANG
Chinese Journal of Epidemiology 2021;42(3):544-548
		                        		
		                        			
		                        			Objective:To evaluate the value of measles IgG antibody avidity assay in identifying the measles cases.Methods:Data from the Measles Surveillance Information System was used to collect laboratory confirmed or discarded cases in 2013-2015, and then tracing back the blood specimens from all measles network laboratories in Tianjin. Measles antibody avidity assay was used to detect and to redefine cases from the discarded ones.Results:A total of 326 measles cases including 267 laboratory-confirmed and 59 discarded cases were enrolled into this study, with 92.33% (301/326) of them aged ≥20 years. Result from the measles IgG antibody avidity assay showed that the ratio of high-avidity was 91.23%(52/57) of the discarded cases, which was significantly higher than 66.95% (158/236) of the laboratory confirmed cases ( χ2=13.33, P<0.001). According to the case criterion, 15.25% (9/59) of the discarded cases were redefined as measles cases. Eight out of the nine cases were high-avidity with measles containing vaccine (MCV) vaccination history that named as SVF cases. One in nine cases with low-avidity was with typical clinical symptomatic measles but with no vaccination history of MCV. Conclusion:Measles IgG antibody avidity assay could provide reference serological evidence to reduce the error from those discarded cases caused by false negative results on IgM antibody, when diagnosing the measles cases.
		                        		
		                        		
		                        		
		                        	
9.Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease
Yifeng SUN ; Haoyao JIANG ; Haiyong GU ; Yi HE ; Yu YANG ; Xiaobin ZHANG ; Yang YANG ; Rong HUA ; Xufeng GUO ; Bo YE ; Teng MAO ; Zhigang LI
Chinese Journal of Surgery 2020;58(9):691-696
		                        		
		                        			
		                        			Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.
		                        		
		                        		
		                        		
		                        	
10.Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease
Yifeng SUN ; Haoyao JIANG ; Haiyong GU ; Yi HE ; Yu YANG ; Xiaobin ZHANG ; Yang YANG ; Rong HUA ; Xufeng GUO ; Bo YE ; Teng MAO ; Zhigang LI
Chinese Journal of Surgery 2020;58(9):691-696
		                        		
		                        			
		                        			Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.
		                        		
		                        		
		                        		
		                        	
            
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